We have found that neurons in the nucleus accumbens inhibit VTA dopamine neurons through GABAB receptor activation while inhibiting VTA GABA neurons through GABAA receptors. The activation of GABAB receptors by nucleus accumbens inputs is sufficient to pause spiking in VTA dopamine neurons. Using optogenetic manipulations, cell-type specific lesions, and slice electrophysiology, we have shown that dynorphin-containing neurons in the nucleus accumbens are both necessary and sufficient for the activation of GABAB receptors in dopamine neurons. We have also shown that multiple neuromodulators can increase or decrease the strength of inhibitory transmission in this pathway. Currently, we are attempting to delete GABAB receptors to examine their role in naturalistic and addictive behaviors.